RAIL Score Provides Useful, Noninvasive Biomarker for Renal Disease Activity

Analysis of urine samples from patients in a phase 2 and phase 3 trial is offering clinicians with new insight into the utility of the renal activity index for lupus (RAIL) score.

Results of the study, which was presented at the Congress of Clinical Rheumatology (CCR) East 2023 annual meeting, indicate use of the creatinine-standardized RAIL (RAIL-Cr) score could help identify patients with active renal disease in those with systemic lupus erythematosus (SLE) and differentiate responders and nonresponders to lupus nephritis treatments.¹

“RAIL-Cr identifies adult SLE patients with active renal disease. Longitudinal RAIL-Cr scores differentiate responders and non-responders to lupus nephritis treatment. RAIL-Cr has novel clinical utility as a non-invasive biomarker signature to monitor treatment response over time,” wrote investigators.¹

The current study led by Hermine Brunner, MD, MSc, director of the Division of Rheumatology at Cincinnati Children’s Hospital Medical Center, with intent of developing a better understanding of the potential utility of the RAIL score. With this in mind, Brunner and fellow investigators designed their analysis leveraging data from the phase 2 MUSE and phase 3 TULIP-1 trial.¹

MUSE was a phase 2 randomized, double-blind, placebo-controlled trial designed to compare the effects of anifrolumab 300 mg, anifrolumab 1000 mg, or placebo every four weeks for the treatment of moderate to severe SLE. The trial met its primary and secondary endpoints, with anifrolumab treatment associated with significantly greater rates of improvement for multiple composite and organ-specific disease activity measures.²

The phase 3 TULIP-1 trial was a randomized, double-blinded, 52-week placebo-controlled, multicenter trial designed to compare effects of 150mg anifrolumab, 300mg anifrolumab, or placebo every 4 weeks among a cohort of patients with SLE.³ Of note, these trials, along with the phase 3 TULIP-2 trial, would go on to serve as the basis for the August 2021 approval of anifrolumab (Saphnelo) for moderate to severe SLE.⁴

As part of the MUSE trial, investigators collected urine samples at baseline and again at weeks 12, 24, and 48 from patients with biopsy-proven active Class III and IV lupus nephritis. As part of TULIP-1, investigators collected urine samples at baseline from a subset of patients with active, nonrenal SLE and renal BILAG scores C, D, or E.¹

A total of 131 lupus nephritis patients were included in the study. This cohort was 43% White, 83% were female, and the median age was 34 years. At baseline, this cohort had a median proteinuria of 2.62 (Interquartile range [IQR], 1.53-4) mg/dL, a median estimated glomerular filtration rate (eGFR) of 91.8 (IQR, 63.1-125), and a median RAIL-Cr score of 5.59 (IQR, 4.31-6.47). A total of 59 patients were included from the SLE study. This cohort was 76% White, 93% were female, the median age was 36 years, and the median nonrenal SLEDAI-2k score was 12. Investigators noted the RAIL-Cr scores were higher among the lupus nephritis group than among the SLE group (P <.001).¹

Investigators pointed out receiver operator characteristic (ROC) analyses were conducted assessing the ability of RAIL scores to distinguish patients with renal activity and involvement. Additionally, for the purpose of analysis, patient RAIL-Cr scores from the lupus nephritis were compared between nonresponders and patients with complete renal response (CRR), partial renal response (PRR), and a urine protein-creatinine ratio (UPCR) decrease of 50% or more.¹

A CRR was defined as 24-hour UPCR equal to or less than 0.7 mg/mg, an eGFR of 60 ml/min/1.73m2 or greater, or a 20% or more decrease, no treatment discontinuation, and no restricted medication use. A PRR was defined as improvement in 24-hour UPCR to less than 1 mg/mg, if baseline UPCR was 3 mg/mg or less, and to 3.0 mg/mg or less, if baseline UPCR was 3 mg/mg or greater, and an improvement of 50% or greater was required.¹

Upon analysis, ROC analyses revealed an area under the curve of 0.8, with an odds ratio of log-transformed RAIL at 2.03. Among those in the lupus nephritis trial at weeks 12, 24, an 52, results incite there were 25, 31, and 41 patients with CRR, 39, 54, and 60 with PRR, and 40, 73, and 77 with UPCR50, respectively. Investigators also highlighted a significant difference was observed for RAIL-Cr scores among responses and on responders at weeks 12, 24, and 48 in a Wilcoxon rank sum test.¹

References:

1. Brunner HI, Lindholm C, Cody E, et al. The Renal Activity Index for Lupus (RAIL) Identifies Active Renal Disease in SLE Patients and its Longitudinal Score Associates with Renal Responses in Lupus Nephritis. Paper presented at: Paper presented at: Congress of Clinical Rheumatology (CCR) East 2023 Annual Meeting. Destin, FL. May 4 – 7, 2023.
2. Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017;69(2):376-386. doi:10.1002/art.39962
3. Update on TULIP 1 Phase III trial for anifrolumab in systemic lupus erythematosus. AstraZeneca Media Centre. https://www.astrazeneca.com/media-centre/press-releases/2018/update-on-tulip-1-phase-iii-trial-for-anifrolumab-in-systemic-lupus-erythematosus-31082018.html. Published August 31, 2018. Accessed May 6, 2023.
4. Saphnelo (anifrolumab) approved in the US for moderate to severe systemic lupus erythematosus. AstraZeneca Media Centre. https://www.astrazeneca.com/media-centre/press-releases/2021/saphnelo-approved-in-the-us-for-sle.html. Published August 2, 2021. Accessed May 6, 2023.